A Case Report and a Review of TRAPPC4-Related TRAPPopathy

Area of Science:

• Genetics
• Neuroscience
• Rare Diseases

Background:

• Neurodevelopmental disorder with spasticity, epilepsy and brain atrophy (NEDESBA) is a rare autosomal recessive condition.
• It is associated with pathogenic variants in the TRAPPC4 gene, part of the TRAPP complex crucial for cellular functions.
• TRAPPopathies present overlapping clinical features like microcephaly, epilepsy, and intellectual disability.

Purpose of the Study:

• To report a case of NEDESBA in a 13-month-old male with unique symptoms.
• To highlight the diagnostic challenges due to phenotypic overlap with metabolic disorders.
• To emphasize the importance of early molecular genetic testing.

Main Methods:

• Clinical case presentation of a pediatric patient.
• Biochemical screening for metabolic disorders (biotinidase deficiency).
• Whole exome sequencing to identify the genetic variant.

Main Results:

• The patient presented with epileptic spasms, neurodevelopmental delay, hair loss, and skin rashes.
• Initial metabolic screening suggested biotinidase deficiency, but it was ruled out.
• Whole exome sequencing identified a homozygous splice-site variant (c.454+3A>G) in the TRAPPC4 gene, confirming NEDESBA.

Conclusions:

• The case highlights the phenotypic variability and overlap of NEDESBA with metabolic disorders.
• Early molecular testing is essential for accurate diagnosis of NEDESBA.
• TRAPPC4 variants are a significant cause of rare neurodevelopmental disorders, particularly in consanguineous populations.